Using the hereditary obese hyperglycemic syndrome as our main model for the study of the relationship between obesity and maturity-onset diabetes, we shall continue to examine the characteristics of insulin binding in adipose tissue, and the effect of insulin on glycerol kinase activity in the adipose cells. (Glycerol kinase activity, normally very low in white adipose tissue, is high in the obese hyperglycemic syndrone and may be responsible, in turn, for a variety of biochemical abnormalities in this syndrome.) We shall examine also the mechanism of the inability of these animals to adequately mobilize lipids in fasting (leading to a pronounced negative nitrogen balance on "reducing" diets) and to step up lipid oxidation in the cold (leading to extreme sensitivity to cold, hypothermia and death). We shall examine further the role of possible pancreatic factors in the etiology of the obese hyperglycemic syndrome through a variety of surgical and transplant techniques. We shall make comparative studies on New Zealand obese mice and db/db mice (other forms of genetic obesity with diabetes), Zucker fatty rats (normal blood sugar but high insulin) and gold thioglucose, hypothalamically lesioned obese mice (a form of obesity without diabetes and primary metabolic abnormality, first extensively studied here). We shall investigate the effects on lipolysis of fasting conditions and of a cold environment, the levels of blood glucose, circulating and pancreatic insulin and pancreatic histology and the insulin resistance in relation to insulin binding to fat cell membranes in these various animal models. We shall also examine the mechanism of development of obesity in those strains of rodents (such as C3H and A/F strains of mice, and the sand rat) which become obese when fed high fat diets while regulating their weight on normal diets.